Single photon emission computed tomography (SPECT) has become an important tool in the diagnosis of heart disease, primarily because it has demonstrated an important clinical role in evaluating myocardial ischemia and more recently in evaluating myocardial viability. Over the last several years, (201)Tl has been the primary radiopharmaceutical used for cardiac SPECT. More recently, agents like sestamibi and teboroxime labelled with (99m)Tc have been developed to replace (201)Tl. The isotope(99m)Tc is more desirable than (201)Tl because of its better photon energy and radiation absorbed dose properties. However, these agents have not totally replaced (201)Tl due in part to their physiological characteristics. In particular, teboroxime has a fast wash-in and wash-out from the heart which requires rapid tomographic acquisitions which previously has not been feasible. However, with the advancement of multi- detector SPECT systems, we have demonstrated that dynamic cardiac SPECT imaging of teboroxime is possible. The development of dynamic cardiac SPECT has the potential to offer a more sensitive measure of ischemia than the present static SPECT techniques using (201)Tl. The goal of this proposal is to prescribe clinical protocols for dynamic SPECT imaging of the heart that are able to acquire complete projection sets every 5-10 seconds of a full three-dimensional tissue distribution of a short biological half-life radiopharmaceutical and to develop mathematical tools to extract from the dynamically acquired data a three- dimensional spatial distribution of kinetic parameters in the left ventricular myocardial tissue of blood volume fraction and wash-in (k21) and wash-out (k12) rate constants. The proposal will develop the applied mathematical tools to accurately and precisely quantify kinetic parameters and systematically evaluate these methods with computer simulations, canine experiments and clinical studies. At the completion of this proposal equipment requirements will also be specified. This proposal draws upon the physiological modeling development in PET. At present, PET is much further advanced than SPECT in utilizing dynamic imaging to extract kinetic parameters of organ systems. It is the intent of this proposal to develop methods that would be able to use existing multi-detector SPECT systems; and, in so doing, to provide improved health care to the general public through better detectability of myocardial infarcts, better diagnosis of ischemic heart disease, and better evaluation of tissue viability without adding additional cost to the SPECT procedure. Many of the methods developed will also be applicable to other organ systems such as the kidney and the brain.